The Brite Side of TRPV1: Novel Role in Browning of White Adipocytes

Abstract

Obesity foreshadows metabolic syndrome. Sedentary life style and high calorie intake lead to obesity. Therefore, a strategy to prevent obesity and facilitate weight-loss is an urgent need. In an effort to achieve this goal, we report that dietary capsaicin (CAP; 0.01%) inhibited weight gain in high fat diet (HFD; 60% calories from fat)-fed wild type mice but not those genetically lacking transient receptor potential vanilloid 1 (TRPV1-/-), without modifying ad libitum food or water intake. HFD inhibited TRPV1 expression, activity and facilitated fat accumulation in white adipose tissue (WAT) while dietary CAP antagonized the effects of HFD. Furthermore, introduction of CAP in diet suppressed HFD-induced weight gain in wild type mice. Analyses of mechanisms by which CAP antagonized HFD-induced obesity revealed that HFD suppressed TRPV1 expression and activity in adipocytes and CAP ablated this. Also, CAP significantly increased the expression of (1) brown fat marker genes - uncoupling protein-1, bone morphogenetic protein 8b and peroxysome proliferator activated receptor gamma (PPAR) coactivator-1 (PGC-1); (2) sirtuin 1 (SiRT1; NAD-dependent protein deacetylase - a gene that increases fat metabolism) and (3) PRDM-16 (a gene that regulates browning of white fat and promotes energy expenditure) in WAT of wild type but not TRPV1-/- mice. Consistently, dietary CAP increased metabolic activity of wild type mice. The increase in SiRT1 was associated with a concurrent decrease in acetylated PPAR in inguinal and epididymal adipose tissues, which is important for the recruitment of PRDM-16 to PPAR to induce browning of white adipose tissues. CAP also increased the expression of SiRT1 and PRDM-16 in brown adipose tissue. Collectively, we demonstrate that dietary CAP antagonizes obesity by stimulating the browning of WAT. Our work uncovers the emergence of TRPV1 agonists as new drug candidates to combat obesity.